Long-term recurrence-free survival following total penectomy and additional chemotherapy for solitary penile metastasis from muscle invasive bladder cancer

Abstract

Penile metastasis from bladder cancer is extremely rare and often presents as part of multiple distant metastases. However, no established standard treatment exists for a solitary penile metastasis. We report an 83-year-old male diagnosed with a solitary penile metastasis two years after radical cystectomy for muscle-invasive bladder cancer. Histopathological examination revealed a solitary tumor within the corpus cavernosum consistent with metastatic urothelial carcinoma. The patient underwent total penectomy followed by adjuvant chemotherapy and has remained recurrence-free for seven years. This case illustrates the potential effectiveness of combining radical surgery and chemotherapy in managing a rare penile metastasis from bladder cancer.

Highlights

• •A rare case of a solitary penile metastasis from bladder cancer.
• •The patient underwent total penectomy followed by adjuvant chemotherapy.
• •The patient has remained recurrence-free for seven years.
• •Combined radical surgery and chemotherapy is used to manage rare penile metastasis.

1. Introduction

Bladder cancer commonly metastasizes to the lungs, bones, and liver. Penile metastasis is extremely rare and typically occurs as part of widespread disease. Due to the limited number of reported cases, standard treatment strategies for a solitary penile metastasis remain undefined. We present a rare case successfully treated with total penectomy and adjuvant chemotherapy, resulting in long-term recurrence-free survival.

2. Case presentation

An 83-year-old Asian man was initially diagnosed with bladder cancer, and, due to repeated recurrences, he later underwent laparoscopic radical cystectomy, urethrectomy, bilateral cutaneous ureterostomy, and pelvic lymph node dissection. Preoperative computed tomography revealed a slightly enhanced bladder mass in the left wall. Magnetic resonance imaging (MRI) showed that the tumor was low intensity in T2-weighted images (T2WI) and low intensity in apparent diffusion weighted co-efficient (ADC; Fig. 1A–D). Pathological examination revealed a muscle-invasive high-grade urothelial carcinoma (pT2a; Fig. 1E and F). It also revealed lymphovascular invasion with positive D2-40 and CD34 staining on immunohistochemistry. Surgical margins and ureteral stumps were negative for metastasis, as were the dissected obturator, internal iliac, or external iliac lymph nodes. However, two years later, a firm nodule was noted at the penile base, and CT revealed the isolated enhanced mass in penis. An MRI showed a mass of diffuse signal reduction in the corpus cavernosum penis with hyperintense structures on T2WI (Fig. 2A). The mass demonstrated diffusion restriction on diffusion-weighted images and ADC mapping (Fig. 2B and C). No other distant metastases were identified, and with a diagnosis of a solitary penile metastasis, a total penectomy was performed (Fig. 3A–C). Histopathological examination revealed a solitary tumor within the corpus cavernosum surgical margins were negative. Pathological findings in HE clearly revealed that nests of atypical urothelial cells infiltrating the corpus cavernosum, the subepithelial tissue of the penis, and the periurethral adipose tissue, consistent with recurrent urothelial carcinoma. (Fig. 3D and E). Considering his age, adjuvant chemotherapy with 80% dose of gemcitabine (1000 mg/m² on days 1, 8, and 15) and 80% dose of cisplatin (70 mg/m² on day 2) was administered over three cycles, with no notable adverse events. The patient has remained recurrence-free for seven years following surgery.

Fig. 1.

Imaging study and pathological findings at radical surgery (A) Axial computed tomography (CT) showing focal thickening of the posterior bladder wall (arrow heads ▷). (B) Contrast-enhanced axial CT demonstrating enhancement in the same region. (C) T2-weighted magnetic resonance imaging (MRI) showing a hypointense lesion in the posterior bladder wall. (D) Apparent diffusion coefficient (ADC) map showing corresponding hypointensity. (E) Hematoxylin and eosin (H&E) staining ( × 4): Nests and cords of atypical urothelial carcinoma cells infiltrating the superficial muscularis propria. (F) H&E staining ( × 40): Marked nuclear atypia with chromatin clumping.

Fig. 2.

Imaging study when penile metastasis was detected. (A) T2-weighted magnetic resonance imaging (MRI) showing a well-defined, 24-mm hypointense nodule in the right corpus cavernosum. (B) Diffusion-weighted imaging (DWI) showing high signal intensity in the same lesion. (C) Apparent diffusion coefficient (ADC) map showing corresponding hypointensity.

Fig. 3.

Findings in surgery of penile tumor. (A) Gross appearance of a firm, poorly mobile nodule at the base of the penis. (B) Post-penectomy specimen confirming complete tumor resection. (C) Macroscopic view showing a well-circumscribed, yellowish-white tumor (30 mm) within the corpus cavernosum. (D) Hematoxylin and eosin (H&E) staining ( × 4): Nests of atypical urothelial carcinoma cells infiltrating the periurethral adipose tissue. (E) H&E staining ( × 40): Marked nuclear atypia with chromatin condensation.

3. Discussion

This case illustrates long-term recurrence-free survival after total penectomy and adjuvant chemotherapy for a solitary penile metastasis from muscle-invasive bladder cancer. Penile metastases are uncommon, most often arising from bladder or prostate primaries; they commonly present as part of disseminated disease with a poor prognosis.¹ Aggregated English-language literature reports approximately 480 cases, with primary sites distributed predominantly in the genitourinary tract (69.8%, mainly bladder and prostate), followed by the gastrointestinal tract (21.1%), and respiratory sites (a few percent).² Because many patients harbor systemic disease at presentation, the treatment goal is often palliative.¹ By contrast, when thorough staging demonstrates true isolation of the cancer to the penis, curative-intent resection becomes a reasonable strategy. In our patient, comprehensive imaging revealed no extra-penile disease, supporting total penectomy with curative intent. Prior reviews note that, in carefully selected patients with disease confined to the penis, surgery can yield the most favorable outcomes.¹ When limited disease can be diagnosed based on appropriate imaging studies, total penectomy might likely to be an important surgical strategy.

Pathologically, the penectomy specimen confirmed metastatic urothelial carcinoma with negative margins, enhancing the likelihood of durable local control. The prior cystectomy specimen had shown lymphovascular invasion, features that clinically imply a higher risk of systemic relapse in patients who do not receive neoadjuvant therapy. Consequently, adding systemic therapy after a complete resection was a rational choice. From a systemic perspective, cisplatin-based combination chemotherapy improves survival in metastatic urothelial carcinoma. Randomized trials have shown that neoadjuvant cisplatin-based combinations improve survival in muscle-invasive disease. Adjuvant trials have historically been underpowered but adjuvant therapy may be considered when neoadjuvant therapy was not given and clinical risk is high.³ In addition, complete responses with chemotherapy alone have been described in rare cases of solitary penile metastasis, underscoring potential chemosensitivity in selected settings.⁴ Gemcitabine plus cisplatin was selected because it remains a standard cisplatin-based regimen for urothelial carcinoma. In elderly patients or in those with borderline fitness, clinicians may modify cisplatin scheduling to improve tolerability while maintaining antitumor activity. Contemporary practice considers renal function, performance status, neuropathy, hearing loss, and cardiac status when determining cisplatin suitability. In the present case, despite being 83 years old, the patient had a preserved performance status (ECOG-PS 0), adequate renal function (eGFR 83mL/min/1.73m²), and no grade ≥2 neuropathy, clinically relevant hearing loss, or severe heart failure. And no major contraindications to platinum-based chemotherapy. These factors, together with the absence of other metastatic lesions, supported an aggressive multidisciplinary approach including cisplatin-based chemotherapy. As a result, three cycles of gemcitabine–cisplatin after R0 penectomy were followed by long-term recurrence-free survival, supporting the concept that aggressive local therapy plus systemic treatment can provide durable disease control of highly selected solitary lesions. From a prognostic standpoint, pooled cohorts describe overall poor outcomes in penile metastasis, with ∼50% mortality within one year of diagnosis.² Hori S et al. reviewed and summarized the 21 cases of penile metastasis of urothelial carcinoma, and multidisciplinary treatment approach resulted in long-term remission in one case.⁵ Further investigation of this rare disease is required. Against this background, the patient's seven-year recurrence-free course substantially exceeds typical expectations. This favorable outcome likely reflects the lesion's solitary nature, complete resection with negative margins, and platinum-based postoperative chemotherapy.

4. Conclusion

Our experience supports considering an aggressive multidisciplinary approach—surgery plus systemic chemotherapy—for highly selected patients with isolated penile metastasis.

CRediT authorship contribution statement

Daiki Ishikawa: Writing – original draft, Data curation, Conceptualization. Taku Naiki: Writing – review & editing, Supervision. Aya Naiki-Ito: Writing – review & editing. Hiroko Suzuki: Writing – review & editing. Yohei Tsubouchi: Writing – review & editing. Nobuhiko Shimizu: Writing – review & editing. Toshiharu Morikawa: Writing – review & editing. Maria Aoki: Writing – review & editing. Masakazu Gonda: Writing – review & editing. Noriyasu Kawai: Writing – review & editing. Yukihiro Umemoto: Writing – review & editing. Takahiro Yasui: Writing – review & editing, Supervision.

Informed consent

Written informed consent was given by the patient for the publication of this article and accompanying images.

Statement of ethics

This study was approved by ethics committees of Nagoya City University Graduate School of Medical Sciences. Written informed consent was acquired according to the World Medical Association Helsinki Declaration (in 1975) (IRB No. 60-25-0071).

Funding

None.

Conflict of interest

The authors declare no conflicts of interest.